Navigation Links
Flu virus wipes out immune system's first responders to establish infection
Date:10/20/2013

CAMBRIDGE, Mass. (October 20, 2013) -- Revealing influenza's truly insidious nature, Whitehead Institute scientists have discovered that the virus is able to infect its host by first killing off the cells of the immune system that are actually best equipped to neutralize the virus.

Confronted with a harmful virus, the immune system works to generate cells capable of producing antibodies perfectly suited to bind and disarm the hostile invader. These virus-specific B cells proliferate, secreting the antibodies that slow and eventually eradicate the virus. A population of these cells retains the information needed to neutralize the virus and takes up residence in the lung to ward off secondary infection from re-exposure to the virus via inhalation.

On the surface of these so-called memory B cells are high-affinity virus-specific receptors that bind virus particles to reduce viral spread. While such cells should serve at the body's first line of defense, it turns out that flu virus exploits the specificity of the cells' receptors, using them to gain entry, disrupt antibody production, and ultimately kill the cells. By dispatching its enemies in this fashion, the virus is able to replicate efficiently before the immune system can mount a second wave of defense. This seemingly counter-intuitive pathway to infection is described this week in the journal Nature.

"We can now add this to the growing list of ways that the flu virus has to establish infection," says Joseph Ashour, a co-author of the Nature paper and a postdoctoral researcher in the lab of Whitehead Member Hidde Ploegh.

"This is how the virus gains a foothold," adds Ploegh lab postdoc Stephanie Dougan, also a co-author of the study. "The virus targets memory cells in the lung, which allows infection to be established -- even if the immune system has seen this flu before."

Discovering this dynamic of the virus was no small task, in part because virus-specific B cells are found in exceedingly small numbers and are extremely difficult to isolate. To overcome these challenges, Dougan together with students Max Popp and Roos Karssemeijer leveraged a protein-labeling technology developed earlier in the Ploegh lab to attach a fluorescent label to influenza virus, thus identifying flu-specific B cells by their interaction with fluorescent flu micelles. This step was essential because no flu protein can be tagged in the conventional manner with green fluorescent protein (GFP) in the context of an infectious virus. Dougan then introduced the B cells' nuclei into enucleated mouse egg cells via somatic cell nuclear transfer (SCNT) -- a cloning technique she learned in Whitehead Founding Member Rudolf Jaenisch's lab -- to generate a line of mice with virus-specific B cells and cell receptors.

Though complicated, the generation of mice with B cells specific for a known pathogen allowed Dougan and Ashour to track the virus's interactions with the cells in unprecedented fashion. Because the infectious process they discovered is likely not exclusive to influenza virus, these scientists believe their approach could have implications for other viruses as well.

"We can now make highly effective immunological models for a variety of pathogens," says Dougan. "This is actually a perfect model for studying memory immune cells."

Adds Ashour: "This is research that could help with rational vaccine design, leading to more effective vaccines for seasonal flu. It might even suggest novel strategies for conferring immunity."


'/>"/>

Contact: Matt Fearer
fearer@wi.mit.edu
617-452-4630
Whitehead Institute for Biomedical Research
Source:Eurekalert

Related biology news :

1. Studies reveal structure of EV71, a virus causing childhood illnesses
2. Discovery provides blueprint for new drugs that can inhibit hepatitis C virus
3. To drive infections, a hijacking virus mimics a cells signaling system
4. Scripps Research Institute scientists find promising vaccine targets on hepatitis C virus
5. Harmless human virus may be able to boost the effects of chemotherapy
6. Researchers identify Achilles heel of dengue virus, target for future vaccines
7. Recapitulation of the entire hepatitis C virus life in engineered mouse cell lines
8. BGI, GMU, Mass. Eye and Ear and OUHSC announce agreement to sequence 100 human adenoviruses
9. Berkeley Lab scientists generate electricity from viruses
10. Virus barcodes offer rapid detection of mutated strains
11. Army study: DNA vaccine and duck eggs protect against hantavirus disease
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/19/2017)... New York , April 19, 2017 ... competitive, as its vendor landscape is marked by the ... the market is however held by five major players ... Safran. Together these companies accounted for nearly 61% of ... of the leading companies in the global military biometrics ...
(Date:4/11/2017)... , April 11, 2017 Crossmatch®, ... secure authentication solutions, today announced that it has ... Advanced Research Projects Activity (IARPA) to develop next-generation ... program. "Innovation has been a driving ... Thor program will allow us to innovate and ...
(Date:4/5/2017)... , April 5, 2017  The Allen Institute ... Allen Cell Explorer: a one-of-a-kind portal and dynamic digital ... 3D imaging data, the first application of deep learning ... human stem cell lines and a growing suite of ... platform for these and future publicly available resources created ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... , ... Disappearing forests and increased emissions are the main causes of the ... Especially those living in larger cities are affected by air pollution related diseases. , ... pollution-affected countries globally - decided to take action. , “I knew I had to ...
(Date:10/10/2017)... ... October 10, 2017 , ... ... (ADC) therapeutics, today confirmed licensing rights that give it exclusive global access ... developed in collaboration with Children’s Hospital Los Angeles (CHLA). Additionally, an ...
(Date:10/10/2017)... , Oct. 10, 2017 SomaGenics announced ... the NIH to develop RealSeq®-SC (Single Cell), expected to ... profiling small RNAs (including microRNAs) from single cells using ... highlights the need to accelerate development of approaches to ... "New techniques for measuring levels of ...
(Date:10/9/2017)... ... , ... The award-winning American Farmer television series will feature 3 Bar Biologics ... at 8:30aET on RFD-TV. , With global population estimates nearing ten billion people ... to feed a growing nation. At the same time, many of our valuable resources ...
Breaking Biology Technology: